Incidence and Prevalence of Early-Onset Dementia in Finland

Objectives Current epidemiologic data of early-onset dementia (EOD), characterized by the onset of the disease before the age of 65, are notably scarce. Methods We evaluated the incidence (from January 2010 to December 2021) and prevalence (on December 31, 2021) of EOD and its subtypes in 2 defined areas in Finland. All visits at the dementia outpatient clinics were manually retrospectively reviewed and reassessed (N = 12,490). Results In the population aged ≤65 years, crude incidence of EOD was 12.3/100,000 persons at risk/year based on 794 new cases from January 1, 2010, to December 31, 2021. Incidence rates for EOD were 20.5 and 33.7 per 100,000 person years in the age group of 30–64 and 45–64 years, respectively. The prevalence of EOD was 110.4 in the age group of 30–64 years and 190.3 in the age group 45–64. Alzheimer disease (AD) (48.2%) and behavioral variant frontotemporal dementia (12.7%) were the most frequent subtypes. The incidence of AD increased during the follow-up, whereas incidence of other forms of EOD remained stable. Discussion We found higher incidence rates of EOD than previously reported. Unlike other forms of EOD, the incidence of early-onset AD seems to be increasing.


Introduction
The growing prevalence of dementia presents substantial challenges for public health and economy, with estimated costs soaring to 1,313.4 billion US dollars globally. 1 Approximately 10% of dementia is diagnosed at young age (≤65 years), categorized as early-onset dementia (EOD). 2,3 the era of emerging disease-modifying drugs for Alzheimer disease (AD) 4 and other forms of dementia, access to up-to-date epidemiologic data for these disorders becomes increasingly crucial.Effective health policy planning and the design of new drug trials for neurodegenerative diseases rely on accurate and updated real-world epidemiologic data.
The existing epidemiologic data of EOD 2,5,6 are of limited applicability due to small sample size or nonavailable reviews of clinical diagnoses, that is, diagnoses often rely on singletime-point register collections.Furthermore, register-based analyses are difficult to validate considering diagnostic accuracy or whether the initially diagnosed disease correctly represents the natural progression of the condition.
This study provides up-to-date valid numbers for the incidence and prevalence of EOD.We systematically collected all EOD clinical diagnoses from 2 university hospital districts in the defined areas of Finland.

Standard Protocol Approvals, Registrations, and Patient Consents
This study represents a noninterventional registry study, and no additional data were collected directly from the study individuals.The Finnish Law (552/2019) does not mandate consent for retrospective studies without patient contact, so no Ethical Committee evaluation was needed.Finnish Social and Health Data Permit Authority Findata approved the research protocol (THL/2841/14.02.00/2022).This study is part of DEGE-RWD, research project (NCT06209515), coordinated by Neurocenter Finland.

Study Cohorts and Clinical Review
We conducted an epidemiologic study in the provinces of Northern Ostrobothnia (37,149 km 2 ) located in Northern Finland and Northern Savonia (20,367 km 2 ) in Eastern Finland in the 30-64-year-old inhabitant populations of 174,249 and 106,579, respectively, on December 31, 2021.Kuopio University Hospital (KUH) and Oulu University Hospital (OUH) represent tertiary level neurologic clinics in these areas and are the primary regional referral centers for all citizens ≤65 with neurodegenerative disease-related cognitive complaints.Thus, the EOD diagnostics are performed exclusively within these 2 centers.All patients admitted to KUH  No statistical significance between male and female patients.a The exact number of individuals is not displayed if it is fewer than 3 people to ensure the privacy of individuals.
12.3/100,000 persons at risk/year in the population aged 0-65.The incidence for persons at risk was 20.5/100,000 and 33.7/100,000 in the populations aged 30-64 years and 45-64 years, respectively.The incidences for different age groups and sexes are presented in Table 2.In the population aged 30-64 years, the European Standard Population agestandardized incidence rate was 17.8/100,000 and the World Standard Population adjusted incidence rate was 15.1/ 100,000.During the study period of 12 years, the incidence of early-onset AD increased progressively, while the incidence rates of other forms of EOD remained relatively stable (Figure 1).The prevalences for different age groups for male and female patients are presented in Table 2.No statistical significance was seen between sexes.The incidence and prevalence numbers for distinct clinical phenotypes of EOD are presented in eTable1.

Discussion
8][9] Notably, our World Standard Population age-adjusted incidence rate (15.1/ 100,000 for 30-64-year population) and the European Standard Population age-adjusted incidence rate (17.8/100,000 for the population aged 30-64 years) were also higher than the rates calculated in a recent meta-analysis for the same age group (11/100,000 and 14.4/100,000, respectively). 5The higher incidence rates in our study may reflect the study methodology, which enabled us to detect close to all EOD cases from the study areas.Of interest, the incidence rates of early-onset AD increased steadily, while the incidence figures of other forms of EOD remained relatively stable during the study period.Since the diagnoses were carefully reviewed and classified to diagnostic groups by using uniform criteria, and the incidence numbers for other causes of dementia did not increase, our results may indicate real increase of early-onset AD.However, it might be partly due to the advancements in the awareness or diagnostics, for instance the increased use of CSF biomarkers.
The crude prevalence rates were higher in our study compared with the Norwegian study. 10When comparing ageadjusted numbers, our World Standard Population adjusted prevalence for the population aged 30-64 years (82.2/100,000) was lower than the rate reported in a large meta- analysis (119.0/100,000). 6However, most of the studies in this meta-analysis reported prevalence of EOD only in the age group of 40-65 years, while only a few studies had evaluated the prevalence in younger age groups.
As strengths, we consider the 12-year duration of data collection (encompassing substantial 6,467,028 person-years of the referenced population) and the health care system structure in Finland resulting in the 2 university hospitals serving as centers for all suspected patients with EOD.Furthermore, every diagnosis was thoroughly reassessed, and all the health care visits following the initial diagnosis were taken into account.Moreover, public hospitals in Finland are known for their high quality in diagnosing EOD, including MRI and/ or PET imaging, usually CSF analysis of AD biomarkers, and comprehensive neuropsychological assessments.
As limitations, some cases might have been missed because of loss of insight and thus patient not being referred for diagnostic evaluations.However, this is unlikely due to the regular health checks at occupational health care or mandatory health checks for unemployed people.Furthermore, the social security system of Finland mandates medical diagnosis to justify societal benefits, such as pensions.
In conclusion, our findings suggest higher overall EOD incidence than previously reported, and steadily increasing incidence rate of specifically AD during the study period.

Figure 1
Figure 1 Predicted Incidence by Age and New Early-Onset Dementia Cases by Diagnosis Group, 2021-2021

Table 1
Primary Diagnoses in the Sample (n = 794) a Abbreviations: F = female; M = male.a The exact number of individuals is not displayed if it is fewer than 3 people to ensure the privacy of individuals.tistics at the end of year 2021 as the denominator, whereas all individuals with a diagnosis of EOD alive and aged ≤65 on December 31, 2021, were included in the numerator.For more detail on statistical analyses, see Supplementary File (eMethods).

Table 1 .
Of the patients with AD, 62.2% had CSF amyloid and tau biomarkers measured, indicating AD pathology.
Based on 794 new cases between January 1, 2010, and December 31, 2021, the crude incidence of EOD was

Table 2
Age-Specific and Sex-Specific Incidence in 2010-2021 and Prevalence of Early-Onset Dementia at the End of the Year 2021 in Finland (Northern Ostrobothnia and Northern Savonia Districts)